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HMGCS2 serves as a potential biomarker for inhibition of renal clear cell carcinoma growth
Huajie Mao1, Runzhi Wang2, Fengling Shao2
1Department of Laboratory Medicine, The First Affiliated Hospital of Northwest University, Xi'an No.1 Hospital, Xi'an, 710002, China.
Abstract:
3-Hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) is the rate-limiting enzyme for ketone body synthesis, and most current studies focus on mitochondrial maturation and metabolic reprogramming. The role of HMGCS2 was evaluated in a pan-cancer multi-database using R language, and HMGCS2 was lowly expressed or not differentially expressed in all tumor tissues compared with normal tissues. Correlation analysis of clinical case characteristics, genomic heterogeneity, tumor stemness, and overall survival revealed that HMGCS2 is closely related to clear cell renal cell carcinoma (KIRC). Single-cell sequencing data from normal human kidneys revealed that HMGCS2 is specifically expressed in proximal tubular cells of normal adults. In addition, HMGCS2 is associated with tumor immune infiltration and microenvironment, and KIRC patients with low expression of HMGCS2 have worse prognosis. Finally, the results of cell counting kit 8 assays, colony formation assays, flow cytometry, and Western blot analysis suggested that upregulation of HMGCS2 increased the expression of key tumor suppressor proteins, inhibited the proliferation of clear cell renal cell carcinoma cells and promoted cell apoptosis. In conclusion, HMGCS2 is abnormally expressed in pan-cancer, may play an important role in anti-tumor immunity, and is expected to be a potential tumor prognostic marker, especially in clear cell renal cell carcinoma.
Insights
3-Hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) is often downregulated in cancers. Low HMGCS2 expression correlates with poor prognosis in clear cell renal cell carcinoma (KIRC), suggesting its role in anti-tumor immunity and potential as a prognostic marker.
Area of Science:
- Biochemistry
- Oncology
- Genomics
Background:
- 3-Hydroxymethylglutaryl-CoA synthase 2 (HMGCS2) is the key enzyme in ketone body synthesis.
- Current research primarily focuses on HMGCS2's role in mitochondrial maturation and metabolic reprogramming.
Purpose of the Study:
- To investigate the pan-cancer expression profile of HMGCS2.
- To evaluate the correlation between HMGCS2 and clinical characteristics, genomic heterogeneity, tumor stemness, and patient survival.
- To explore the functional role of HMGCS2 in clear cell renal cell carcinoma (KIRC) progression and anti-tumor immunity.
Main Methods:
- Pan-cancer multi-database analysis using R language.
- Single-cell sequencing of normal human kidney tissues.
- Correlation analysis of HMGCS2 expression with clinical data, genomic features, and immune infiltration.
- In vitro experiments including CCK-8, colony formation, flow cytometry, and Western blot.
Main Results:
- HMGCS2 exhibited low or no differential expression across various tumor tissues compared to normal tissues.
- HMGCS2 expression is significantly associated with clear cell renal cell carcinoma (KIRC), specifically in proximal tubular cells.
- Low HMGCS2 expression in KIRC patients correlates with poorer prognosis, increased tumor stemness, and altered immune microenvironment.
- Upregulation of HMGCS2 suppressed KIRC cell proliferation, promoted apoptosis, and increased tumor suppressor protein expression.
Conclusions:
- HMGCS2 displays abnormal expression in pan-cancer and plays a role in anti-tumor immunity.
- HMGCS2 is a potential prognostic biomarker, particularly for clear cell renal cell carcinoma (KIRC).
- HMGCS2 influences KIRC cell proliferation, apoptosis, and the tumor immune microenvironment.
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